The affinity shown by 67Ga, 111In, and the higher atomic number rare earth radionuclides for nonosseous tumors in man has provided the basis for a diagnostic test (scanning) for the detection of cancer. Our aim in this project is to determine the cellular binding sites for these radionuclides and to identify the nature of the process(es) and the biochemical agent(s) involved. An understanding of the mechanism(s) involved should lead to methods for enhancement of the affinities of these agents for tumor tissue and also to the identification of other tumor-localizing agents of even greater tumor specificity. Our goals for the coming year are: (1) using a new isopycnic sucrose-polyethylene glycol gradient separation and purification technique (in which particle density is altered), we plan to morphologically and enzymatically characterize the microvesicles that are mainly responsible for binding of 67Ga and 111In in hepatoma; (2) We will study the amino acid sequence and carbohydrate content of the 40,000-dalton 67Ga- and 111In-binding glycoprotein found primarily in hepatomas and other tumors and initiate antibody studies of the purified material; (3) Having now solved experimental design problems, the general nature of the effect of the presence of malignancy on the increased body retention of 67Ga in animals following X-irradiation will be assessed, and, if the effect is found to be general, we will initiate an investigation of the sera of tumor-bearing animals for abnormal 67Ga-binding components; and (4) Having determined the characteristics of a new multicompartment interconncting tissue culture system, we will attempt to produce 67Ga- and 111In-subcellular-binding in hepatoma tissue similar to that that is obtained with in vivo labeling by using various organ tissues placed in series with the hepatoma tissue. BIBLIOGRAPHIC REFERENCES: Brown, D.H., Byrd, B.L., Carlton, J.E., Swartzendruber, D.C., and Hayes, R.L. A quantitative study of the subcellular localization of 67Ga. Cancer Res. 36:956-963, 1976. Hayes, R.L. Factors affecting uptake of radioactive agents by tumour and other tissues. In Tumour Localization with Radioactive Agents, IAEA, Vienna, 1976, pp. 29-45.